This proposal addresses the interactions between the sympathoadrenal system (SAS), prostaglandins (PG) and oxytocin (OT) in regulating myometrial activity in sheep. I will study these interactive factors in non pregnant ewes and pregnant ewes both before and during labor. I will combine whole animal in vivo studies with in vitro observations using uterine electromyographic (EMG) recording, radioimmunoassay (RIA), tissue receptor and tissue superfusion techniques. The proposal has five specific aims, to: Specific Aim 1: Investigate the role of the SAS in the initiation and/or modulation of ACTH induced parturition in sheep following chemical sympathectomy. Specific Aim 2: Study the effects of chemical sympathectomy in non-pregnant sheep on: in vivo response of the uterus to phenylephrine, oxytocin and prostaglandins F2 alpha and E2; number of oxytocin, alpha 1, alpha 2, and beta 2 adrenergic receptors; and in vitro production of prostaglandin by uterine tissues. Specific Aim 3: Study the effects of continuous local administration of oxytocin, phenylephrine and the alpha 1 adrenergic antagonist prazosin on: myometrial activity; uterine oxytocin responsiveness; and myometrial oxytocin and alpha adrenergic receptors. Specific Aim 4: Study the responsiveness to oxytocin, phenylephrine and prostaglandins F2 alpha and E2 of isolated myometrial tissue transplanted with or without the underlying endometrium and compare the myometrial responses to the response of the mesometrium. Specific Aim 5: Study the role of endometrial caruncles in the local control of myometrial activity in non pregnant ovariectomized sheep. These studies will provide a better understanding of preterm, term and postterm labor and delivery and lead to more rational therapies, in particular of preterm labor.